Tributyltin in male mice disrupts glucose homeostasis as well as recovery after exposure: mechanism analysis

Abstract

Organotin compounds such as tributyltin (TBT) and triphenyltin can induce diabetes and insulin resistance. However, the development of diabetes caused by organotins and its underlying mechanisms remain unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 μg/kg) once every 3 days for 45 days. Their body weights increased and reached a significant difference compared to the control, and the fasting blood glucose levels were significantly elevated. The fasting levels of serum insulin and adiponectin increased, while glucagon levels decreased in the animals treated with TBT. The expression of the insulin receptor (IR) signaling cascade, including IR, IR substrate, phosphatidylinositol 3-kinase, Akt, and glucose transporter 4, was inhibited both in the skeletal muscle and the liver, which might be a main reason for the hyperglycemia and hyperinsulinemia. After removing the TBT stress for 60 days, the animals which had received exposure to TBT could recover normoglycemia, accompanied with a recovery of the suppressed IR signal pathway and fasting insulin levels. However, the fasting levels of serum adiponectin and glucagon were lower than that of the control mice, which would remain a potential risk inducing the disruption of glucose homeostasis.

Low-dose tributyltin exposure induces an oxidative stress-triggered JNK-related pancreatic β-cell apoptosis and a reversible hypoinsulinemic hyperglycemia in mice

“…Li et al . recently further demonstrated that the hyperglycemia in mice exposed to low-dose TBT for 45 days could be reversed after removing the TBT exposure for 60 days 31 . In the present study, we found that a 4-week consecutive exposure to TBT (0.25 mg/kg) in mice caused an increase in fasting blood glucose, a decrease in plasma insulin, and an elevation in glucose intolerance accompanied by a significant increase of plasma lipid peroxidation.…”

Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

“…The physical symptom of insulin resistance might be explained by the apoptosis of islet cells induced by chronic and repeated exposure to TBT. 43 One recent study 44 showed that TBT treatment for 45 days decreased the expression of AKT without induction by exogenous insulin. Different from the above-mentioned paper, we did not detect the change of total AKT expression but observed an alteration of activity by the reduced abundance of phosphorylated AKT in the liver and muscle 8 min after insulin injection after TBT treatment.…”

Association between urinary tin concentration and diabetes in nationally representative sample of US adults

“…Although there are no studies reporting the diabetogenic effects of inorganic tin exposure, the findings of the present study are in line with previous in vitro and in vivo studies showing potential diabetogenic effects of certain organotin compounds. 4,26 Animal studies have consistently found that organotin compounds, such as tributyltin, could impair pancreatic function, 13,14 induce insulin resistance, 15,27 and disrupt glucose homeostasis. 28 Tributyltin can induce hepatic inflammation and lipid storage by stimulating peroxisome proliferatoractivated receptor gamma (PPARγ) and inhibiting the estrogen receptor (ER)α.…”